tbuckley/cabot-search huggingface dataset:
Abstract A045: Whole transcriptome analysis of paired African American prostate cancer cell lines
Authors: Kristi Y. Lee, Erica L. Beatson, Cindy H. Chau, Douglas K. Price, William D. Figg
Journal: Cancer Research (2023)

Abstract Recent investigations on patient race have begun to characterize biological differences in prostate cancer, particularly among patients of African ancestry. Despite clinical trends continuously demonstrating this health disparity, very few African American cell line models exist for downstream molecular investigations, and even fewer have undergone proper characterization of their expression profiles. Here, we characterize the transcriptome of the non-malignant RC-77 N/E and malignant RC-77 T/E prostate epithelial cell lines previously established from prostate specimens from the same African American patient with early-stage primary prostate cancer. Total RNA sequencing was performed on the paired cell lines using Illumina NextSeq 2000 P2 to build transcriptomic profiles that have previously been undetermined. Following data analysis and normalization, we identified 369 genes with significant upregulation in the RC-77 T/E cell line in comparison to its normal counterpart. Among the top 15 upregulated genes, half of them were previously characterized in prostate cancer but not in the context of patient race. We further compared the transcriptome of RC-77 T/E to that of the African American metastatic MDA-PCa-2b. Finally, we analyzed differential gene expression by race among prostate cancer patients in The Cancer Genome Atlas (TCGA) to correlate our transcriptomics findings on the cell line level with that on the population level. These findings may allow for more targeted assessments of genes that are dependent on race as molecular tools are established to narrow the health disparities gap in prostate cancer. Citation Format: Kristi Y. Lee, Erica L. Beatson, Cindy H. Chau, Douglas K. Price, William D. Figg. Whole transcriptome analysis of paired African American prostate cancer cell lines [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr A045.
Abstract B044: Exosomal cancer-type <i>SLCO1B3</i> and <i>ABCC3</i> as potential biomarkers of castration resistant prostate cancer
Authors: Erica L. Beatson, Kristi Y. Lee, Martina A. Knechel, Elijah R. Sommer, Roger Depaz, Emily N. Risdon, Andres F. Leon, Jonathan D. Strope, Douglas K. Price, Cindy H. Chau, William D. Figg
Journal: Cancer Research (2023)

Abstract Extracellular vesicles (EVs) provide a minimally invasive source of tumor-specific markers for liquid biopsy that can be utilized for cancer detection, diagnosis, or monitoring progression. Our laboratory has previously demonstrated the endogenous expression of all transporter systems in the common prostate cancer cell lines (LNCaP, 22Rv1, PC3, DU-145) using a medium throughput TaqMan-based qRT-PCR assay. We identified the two most differentially expressed transporter genes in castration-resistant prostate cancer cells (CRPC) as the cancer-type solute carrier organic anion transporter family 1B3 (ct-SLCO1B3) and the ATP Binding Cassette Subfamily Member C (ABBC3). Both transporters have been investigated as EV-derived tumor markers; however, their detection in prostate cancer-derived EVs remains to be determined. This study aims to investigate whether ct-SLCO1B31B3 and ABCC3 mRNA exists in prostate cancer-derived EVs and can be further detected using plasma specimens. We isolated EVs from prostate cancer (LNCaP, 22Rv1, PC3, DU-145) cell line supernatant and extracted exosomal RNA for qPCR analyses. Both ct-SLCO1B3 and ABBC3 transcripts were only detected in CRPC-derived EV cells vs androgen-responsive prostate cancer cells. To explore the possibility that both transcripts in CRPC-derived EVs can be detected in plasma, we isolated plasma EVs derived from human prostate cancer xenograft mice, and then performed digital droplet PCR analysis. We demonstrated that ct-SLCO1B3 and ABBC3 are detectable in the DU-145 xenograft mouse model, both in tissues and in plasma-derived EVs. Our results provide evidence that ct-SLCO1B3 and ABCC3 exist in EVs and can be detected (at least) in mouse plasma, potentially supporting their roles as novel, plasma-based biomarkers for monitoring prostate cancer progression. Citation Format: Erica L. Beatson, Kristi Y. Lee, Martina A. Knechel, Elijah R. Sommer, Roger Depaz, Emily N. Risdon, Andres F. Leon, Jonathan D. Strope, Douglas K. Price, Cindy H. Chau, William D. Figg. Exosomal cancer-type SLCO1B3 and ABCC3 as potential biomarkers of castration resistant prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr B044.
Abstract B040: Novel immunotherapy strategies targeting PTEN and TP53 defects in advanced prostate cancer
Authors: Wei Shi, Yin Wang, Yuehui Zhao, Di Zhao
Journal: Cancer Research (2023)

Abstract Prostate cancer is the most diagnosed cancer in men worldwide and the leading cause of cancer death in men worldwide. Genetic inactivation of PTEN and TP53 are common in advanced prostate cancers. Checkpoint immunotherapy has yielded meaningful responses across many cancers but shown modest activity in advanced prostate cancer. Prior studies showed that overexpression of immune checkpoint B7-H3 (CD276) correlates with the increased risks of clinical recurrence, disease spread, and poor outcomes in various cancer types, including prostate cancer. However, the roles of B7-H3 in prostate cancer development and its tumor microenvironment remain unclear, partially due to the lack of tissue-specific deletion mouse models. This gap in knowledge hinders the application of immunotherapy targeting B7-H3 in prostate cancers. To identify PTEN- and p53-associated immune checkpoints, we performed multi-omics analyses of expression patterns of 51 checkpoint molecules in human prostate cancer samples and found that B7-H3 is one of the most significantly overexpressed immune checkpoints in prostate tumors containing PTEN and TP53 genetic inactivation. Mechanistically, we found that the PTEN-AKT pathway co-operates with p53 pathway in modulating B7-H3 expression in cancer cells. In Pten/Trp53 genetically engineered mouse (GEM) models, prostate-specific deletion of Cd276 resulted in markedly delayed tumor progression and reversed immunosuppression in the tumor microenvironment. Furthermore, we developed and evaluated novel combinatorial immunotherapy strategies targeting B7-H3 in advanced prostate cancer with PTEN and TP53 deficiencies. Citation Format: Wei Shi, Yin Wang, Yuehui Zhao, Di Zhao. Novel immunotherapy strategies targeting PTEN and TP53 defects in advanced prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr B040.
Making In Vitro Tumor Models Whole Again (Adv. Healthcare Mater. 14/2023)
Authors: Kenny Zhuoran Wu, Christabella Adine, Aleksandr Mitriashkin, Benjamin Jun Jie Aw, N. Gopalakrishna Iyer, Eliza Li Shan Fong
Journal: Advanced Healthcare Materials (2023)

In Vitro Tumor Models The success of personalized cancer therapy hinges on a timely clinical decision and a preclinical model that can recapitulate tumor and stromal heterogeneity for clinically relevant drug profiling. In article 2202279, Eliza Li Shan Fong and co-workers review how by transcending the existential reductionist approaches, bioengineered patient-derived explant (PDE) models can truly replicate the tumor features in vivo and allow clinicians to rapidly offer and strategize specific care and treatment for each cancer patient.
Abstract A072: Unique mouse models of high-risk prostate cancer adequate for targeted interception
Authors: Anait S. Levenson
Journal: Cancer Research (2023)

Abstract Metastasis-associate protein 1 (MTA1), a master transcriptional co-regulator and chromatin modifier, is strongly associated with clinically aggressive prostate cancer. The loss of MTA1 reduces the aggressiveness and metastatic potential of prostate cancer cells. Preclinical studies with subcutaneous and orthotopic MTA1 knockdown xenograft models have shown the tumor promoting role of MTA1 and associated survival pathways in prostate cancer. However, the exact role of MTA1 in the pathobiology of prostate cancer is unknown. We first generated a conditional mouse with human MTA1 transgene knocked into the mouse Rosa26 locus (R26MTA1; Cre+ ). By crossing a R26MTA1 mouse with a Pten “floxed” mouse, we have created unique high-risk high-grade PIN-prone R26MTA1; Ptenf/+; Cre+ mice and a high-risk R26MTA1; Ptenf/f; Cre+ cohort of mice with characteristics of a castrate-resistant neuroendocrine subtype suitable for early chemoprevention/interception and novel effective therapies, respectively. I will discuss the potent MTA1-targeted anticancer effects of natural stilbenes (resveratrol, pterostilbene, and Gnetin C) observed in the preclinical R26MTA1; Ptenf/+; Cre+ model mimicking high-risk premalignant tumors with overexpressed MTA1. Further, evidence will be provided on the role of MTA1 in castrate resistance and on the neuroendocrine features defining the potential of the R26MTA1; Ptenf/f; Cre+ model in discovering novel chemoimmunotherapies. Our studies demonstrate progress towards successful targeted interception strategies for prostate cancer with an implication for precision medicine. Supported by the NCI/NIH R15CA216070 Award. Citation Format: Anait S. Levenson. Unique mouse models of high-risk prostate cancer adequate for targeted interception [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr A072.
Asthma-protective agents in dust from traditional farm environments
Authors: Mauricius Marques dos Santos, Vadim Pivniouk, Bettina Rankl, Alesia Walker, Giulia Pagani, Norbert Hertkorn, Philippe Schmitt-Kopplin, Christoph Müller, Franz Bracher, Juliane Merl-Pham, Stefanie M. Hauck, Michael Schloter, Ashley N. Michael, Dayna Anderson, Linnea Honeker, Justyna Gozdz, Oksana Pivniouk, Carole Ober, Mark Holbreich, Fernando D. Martinez, Shane A. Snyder, Erika von Mutius, Donata Vercelli
Journal: Journal of Allergy and Clinical Immunology (2023)

BACKGROUND Growing up on traditional European, and U.S. Amish, dairy farms, in close contact with cows and hay, protects children against asthma, and airway administration of extracts from dust collected from cowsheds of those farms prevents allergic asthma in mice. OBJECTIVES This study sought to begin identifying farm-derived asthma-protective agents. METHODS Our work unfolded along two unbiased, independent but complementary discovery paths. Dust extracts from protective and non-protective farms (European and Amish cowsheds vs. European sheep sheds) were analyzed by comparative nuclear magnetic resonance fingerprinting and differential proteomics. Bioactivity-guided size fractionation focused on protective Amish cowshed dust extracts. Multiple in vitro and in vivo functional assays were used in both paths. Some of the proteins thus identified were characterized by in-solution and in-gel SDS-PAGE enzymatic digestion/peptide mapping followed by liquid chromatography/mass spectrometry. The cargo carried by these proteins was analyzed by untargeted liquid chromatography-high resolution mass spectrometry. RESULTS Twelve carrier proteins of animal and plant origin, including the bovine lipocalins Bos d2 and odorant binding protein, were enriched in dust extracts from protective European cowsheds. A potent asthma-protective fraction of Amish cowshed dust extracts (≈0.5% of the total carbon content of unfractionated extracts) contained seven animal and plant proteins, including Bos d2 and odorant binding protein loaded with fatty acid metabolites from plants, bacteria and fungi. CONCLUSIONS Animals and plants from traditional farms produce proteins that transport hydrophobic microbial and plant metabolites. When delivered to mucosal surfaces, these agents might regulate airway responses.
Abstract B052: Prostate cancer prevention is possible thanks to the evaluation of the primary exons of the BRCA1 biomarker in men
Authors: Haboubacar Elhadji Yaou Moussa, Callinis Capo Chichi
Journal: Cancer Research (2023)

Abstract Prostate cancer is a public health concern among 50 year old the men worldwide and its incidence keep rising. It is triggered by genome instability or epigenetic modifications impacting DNA repair and tumor suppression genes and proteins. In African countries, little data is available on prostate cancer and the loss of BRCA1 exons responsible for tumor suppression. It is in this context that we undertook this study, the general objective of which is to assess the association between BRCA1 instability in patients with prostate cancer, These men with prostate cancer usually present with symptoms like nocturia and poor urinary flow, erectile dysfunction and visible hematuria. Citation Format: Haboubacar Elhadji Yaou Moussa, Callinis Capo Chichi. Prostate cancer prevention is possible thanks to the evaluation of the primary exons of the BRCA1 biomarker in men [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr B052.
Advances in the Management of Metastatic Breast Cancer
Authors: William J. Gradishar
Journal: Journal of the National Comprehensive Cancer Network (2023)

Recent advances in the understanding of the molecular underpinnings of metastatic breast cancer have led to the identification of novel therapeutic targets. The latest update to the NCCN Guidelines for Breast Cancer reflects a rapidly evolving treatment landscape, highlighting the growing importance of combination therapies and personalized medicine in managing estrogen-receptor (ER)–positive, HER2-positive, and triple-negative subtypes. For patients with ER-positive disease, the standard of care remains combination therapies involving cyclin-dependent kinase 4/6 inhibitors, endocrine therapy, and PI3 kinase. In patients with HER2-positive disease, the use of fam-trastuzumab deruxtecan-nxki and tucatinib have demonstrated improved outcomes. For those with triple-negative breast cancer, pembrolizumab, PARP inhibitors, and antibody–drug conjugates (eg, sacituzumab govitecan-hziy) have shown activity.
Updates in the Management of Hepatobiliary Cancers
Authors: Mitesh J. Borad
Journal: Journal of the National Comprehensive Cancer Network (2023)

Hepatobiliary cancers are aggressive tumors that affect the liver and biliary tract and are responsible for nearly 550,000 deaths per year. The most common malignancy is hepatocellular carcinoma, and risk factors include viral hepatitis infection, nonalcoholic steatohepatitis, and excessive alcohol use. Other etiologies include Wilson’s disease, α1-antitrypsin deficiency, and cryptogenic cirrhosis. Clinicians should be aware of underlying conditions and how they influence treatment decisions.
Hereditary/Familial Ovarian Cancer: Testing Principles and Risk Management
Authors: Leigha Senter
Journal: Journal of the National Comprehensive Cancer Network (2023)

Although BRCA1 and BRCA2 pathogenic or likely pathogenic variants are a well-established cause of hereditary ovarian cancer, recent studies have brought other homologous recombination repair pathway genes into the limelight. The current NCCN Guidelines reflect the most up-to-date, evidence-based data relating to the risk management of patients who are carriers of BRCA1/2 and/or other variants. Risk-reducing bilateral salpingo-oophorectomy is the current standard of care, but a recommendation for salpingectomy alone may be on the horizon.
Emerging Therapies in the Treatment of Bladder Cancer
Authors: Arlene O. Siefker-Radtke
Journal: Journal of the National Comprehensive Cancer Network (2023)

The advent of targeted agents, such as enfortumab vedotin, erdafitinib, and sacituzumab govitecan, have revolutionized the treatment of metastatic urothelial cancer. Although these novel therapies have demonstrated favorable efficacy outcomes, their toxicity must be carefully monitored. The NCCN Guidelines for Bladder Cancer recommend platinum-based chemotherapy in this clinical context, but the combination of targeted and immunotherapeutic agents may have the potential to replace it as frontline standard of care.
Bilaterality, not multifocality, is an independent risk factor for recurrence in low-risk papillary thyroid cancer
Authors: Pedro Manuel Rodriguez Schaap, Jia Feng Lin, Madelon J H Metman, Koen M A Dreijerink, Thera P Links, H Jaap Bonjer, Els J M Nieveen van Dijkum, Chris Dickhoff, Schelto Kruijff, Anton F Engelsman
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background The impact of multifocality and bilaterality on recurrence in patients with low-risk papillary thyroid cancer (PTC) is relevant when considering patients for a de-escalated treatment strategy: hemithyroidectomy instead of total thyroidectomy followed with or without radioactive iodine. This study aims to analyze contralateral tumor probability in patients treated for low-risk PTC and assess multifocality and bilaterality as possible predictors for recurrence. Methods Patients with low-risk PTC treated with total thyroidectomy followed with or without radioactive iodine in the Netherlands between 2005 and 2015 were included in this study. Patients were identified from the Netherlands Comprehensive Cancer Organization (IKNL) and linked with the nationwide network and registry of Pathology in the Netherlands (PALGA). Contralateral tumor probability and recurrence were assessed. Results Of 791 included patients, 41.8% (331 of 791) had multifocal disease, with 68.9% (228 of 331) of those patients having bilateral disease. The contralateral tumor probability after hemithyroidectomy was 24.6% (150 of 610) for patients with unifocal disease and 43.1% (78 of 181) for patients with multifocal disease. We found a higher trend of recurrence in patients with bilateral disease, regardless of multifocality: in patients with contralateral disease after precompletion diagnosed unifocal disease 7.3% (11 of 150) had recurrent disease, and patients without contralateral disease after precompletion diagnosed multifocal disease 1.9% (2 per 103) had recurrence. Cox regression analysis showed that bilaterality (hazard ratio = 3.621, 95% confidence interval = 1.548 to 8.471) was the sole statistically significant risk factor for recurrence. Conclusion Low recurrence rates are found in patients with either multifocal or bilateral disease with low-risk PTC. Bilaterality should be taken into account when considering these patients for de-escalated treatment strategy.
Enhanced Transdermal Peptide‐Modified Flexible Liposomes for Efficient Percutaneous Delivery of Chrysomycin A to Treat Subcutaneous Melanoma and Intradermal MRSA Infection
Authors: Yue Cai, Yuteng Chu, Yubei Gong, Yulu Hong, Fuhang Song, Hong Wang, Huawei Zhang, Xuanrong Sun
Journal: Advanced Healthcare Materials (2023)

Superficial skin diseases, including skin infections and tumors, are common healthcare burdens. In this study, the in vivo activity of chrysomycin A (CA) is explored, and a transdermal liposomal CA formulation is further constructed for the simultaneous treatment of cutaneous melanoma and cutaneous methicillin-resistant Staphylococcus aureus (MRSA) infection. The prepared liposomes (TD-LP-CA) display a strong antitumor effect with an IC50 value of less than 0.1 µm in B16-F10 cells, suppress the proliferation of MRSA with a minimum inhibitory concentration (MIC) of 1 µm, and eradicate established MRSA biofilms at 10× MIC in vitro. More importantly, TD-LP-CA shows enhanced stratum corneum (SC) penetration, reaching more than 500 µm beneath the skin's surface due to modification with the TD peptide, and demonstrates excellent subcutaneous tumor penetration after skin application in vivo. TD-LP-CA displays an excellent therapeutic effect against intradermal MRSA infection in mice after topical dermal administration, as well as a moderate inhibitory effect on subcutaneous melanoma with a 75% tumor inhibition rate. The liposomes prepared herein can be a promising carrier for transcutaneous CA transfer for the treatment of superficial diseases such as skin tumors and infections due to their ability to overcome the skin barrier.
PRMT5 supports multiple oncogenic pathways in mantle cell lymphoma
Authors: Shelby L. Sloan, Fiona Brown, Mackenzie Long, Christoph Weigel, Shirsha Koirala, Ji-Hyun Chung, Betsy Pray, Lynda Villagomez, Claire Hinterschied, Anuvrat Sircar, JoBeth Helmig-Mason, Alexander Prouty, Eric Brooks, Youssef Youssef, Walter Hanel, Samir Parekh, Wing Keung Chan, Zhengming Chen, Rosa Lapalombella, Lalit Sehgal, Kris Vaddi, Peggy Scherle, Selina Chen-Kiang, Maurizio Di Liberto, Olivier Elemento, Cem Meydan, Jonathan Foox, Daniel Butler, Christopher E. Mason, Robert A. Baiocchi, Lapo Alinari
Journal: Blood (2023)
Consent in Pharmacogenetic Testing
Authors: Yuichi Ando, Tomohiro Terada
Journal: Journal of Clinical Oncology (2023)

In their comments published in the recent issue on pharmacogenetic testing, Baker et al 1 expressed concerns that DPYD pharmacogenetic testing before fluoropyrimidine chemotherapy has not yet been introduced into the standard of care.In addition to outdated information on the package inserts of fluoropyrimidines and clinical guidelines not reflecting updated pharmacogenetic data, they listed barriers that possibly prevent oncologists from ordering the test.Here, we would like to add the consent procedure as another barrier.A survey conducted in the United States between 2015 and 2016 reported that consent procedures varied among laboratories offering pharmacogenetic testing, with approximately two thirds of facilities requiring a patient's signature.
Grade Group 1 Prostate Cancers Exhibit Tumor-defining Androgen Receptor–driven Programs
Authors: Simon Linder, Tesa M. Severson, Koen J.C. van der Mijn, Ekaterina Nevedomskaya, Joseph C. Siefert, Suzan Stelloo, Mark M. Pomerantz, Matthew L. Freedman, Henk van der Poel, Carmen Jerónimo, Rui Henrique, Andries M. Bergman, Wilbert Zwart
Journal: European Urology (2023)
A U.S. Food and Drug Administration–pooled Analysis of Frontline Combination Treatment Survival Benefits by Risk Groups in Metastatic Renal Cell Carcinoma
Authors: Daniel Lee, Haley Gittleman, Chana Weinstock, Daniel Suzman, Erik Bloomquist, Sundeep Agrawal, Michael Brave, Jamie Brewer, Jaleh Fallah, Harpreet Singh, Shenghui Tang, Amna Ibrahim, Richard Pazdur, Julia A. Beaver, Laleh Amiri-Kordestani
Journal: European Urology (2023)